A Double-masked, Placebo-controlled Study With Open-label Period to Evaluate the Efficacy and Safety of MEDI-551 in Adult Subjects With Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 231
- 试验地点
- 1
- 主要终点
- Time to Adjudication Committee (AC)-Determined Neuromyelitis Optica Spectrum Disorder (NMOSD) Attack During RCP
研究概览
简要总结
To compare the efficacy of inebilizumab (MEDI-551) versus placebo in reducing the risk of an neuromyelitis optica/neuromyelitis optica- spectrum disorders (NMO/NMOSD) attack in participants with NMO/NMOSD.
详细描述
Inebilizumab is a genetically engineered humanized monoclonal antibody that binds to the B cell specific surface antigen cluster of differentiation (CD19) resulting in the depletion of B cells. Inebilizumab depletes antibody-secreting plasmablasts and some plasma cells, which are generally CD19 positive and CD20 negative.
The main objective of this study is to determine whether inebilizumab compare to placebo decreases the risk of an attack in participants with NMO/NMOSD.
This is a multicenter, multinational, randomized, double-masked, placebo controlled study with an open-label extension period to evaluate the efficacy and safety of intravenous (IV) inebilizumab in adult participants with NMO/NMOSD. After a screening period, eligible participants will enter a randomized-controlled period (RCP) of maximum 197 days where they will be randomized in a 3:1 ratio to receive either IV inebilizumab or placebo. NMO/NMOSD attacks will be evaluated by the investigator and confirmed against the attack criteria by an independent Adjudication Committee (AC). Participants for whom the attack was confirmed by the AC will be given the option to enroll into an open label period (OLP) with inebilizumab treatment. Participants who complete the RCP without experiencing an attack will be given the option to enroll into an OLP with inebilizumab treatment. The OLP will continue for a minimum of 1 year and a maximum of 3 years after the last participant enter the OLP. All participants who discontinue from the RCP or the OLP will continue in a Safety Follow-up for a total of 12 months from last dose to evaluate the long-term safety of the investigational product.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women 18 years or older with diagnosis of NMO/NMOSD
- •Confirmation of NMO/NMOSD status:
- •AQP4-IgG sero-positive NMO/NMOSD with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years
- •AQP4-IgG sero-negative NMO with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years
- •Able and willing to give written informed consent and comply with the requirements of the study protocol.
- •EDSS <= 7.5 (8 in special circumstances)
- •Men and women of reproductive potential must agree to use a highly effective method of birth control from screening to 6 months after final dose of the investigational product.
排除标准
- •Lactating and pregnant females
- •Treatment with any investigational agent within 4 weeks of screening
- •Known history of a severe allergy or reaction to any component of the investigational product formulation or history of anaphylaxis following any biologic therapy.
- •Known active severe bacterial, viral, or other infection or any major episode of infection requiring hospitalization.
- •History of alcohol, drug, or chemical abuse, or a recent history of such abuse < 1 year prior to randomization
- •Receipt of the following at any time prior to randomization:
- •Alemtuzumab
- •Total lymphoid irradiation
- •Bone marrow transplant
- •T-cell vaccination therapy
- •Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.
- •Receipt of intravenous immunoglobulin (IVIG) within 1 month prior to randomization.
- •Receipt of any of the following within 3 months prior to randomization:
- •Natalizumab (Tysabri®).
- •Cyclosporin
- •Methotrexate
- •Mitoxantrone
- •Cyclophosphamide
- •Tocilizumab
- •History of Hepatitis B and/or Hepatitis C (Hep B/C at screening)
- •Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection
- •History of malignancies, apart from squamous cell or basal cell carcinoma of the skin treated with documented success of curative therapy > 3 months prior to randomization
- •Any concomitant disease other than NMO/NMOSD that required treatment with oral or intravenous steroids at doses over 20 mg a day for over 21 days
研究组 & 干预措施
Placebo/Inebilizumab
Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants will receive IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who enter OLP will receive IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants will have choice to enter in the SFP at any point during RCP or OLP and will be free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants will continue in the SFP for 12 months from last dose of study drug.
干预措施: Inebilizumab (Drug)
Placebo/Inebilizumab
Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants will receive IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who enter OLP will receive IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants will have choice to enter in the SFP at any point during RCP or OLP and will be free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants will continue in the SFP for 12 months from last dose of study drug.
干预措施: Placebo (Other)
Inebilizumab/Inebilizumab
AQP4-IgG sero positive and sero negative participants will IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who enter OLP will receive IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants will have choice to enter in the SFP at any point during RCP or OLP and will be free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants will continue in the SFP for 12 months from last dose of study drug.
干预措施: Inebilizumab (Drug)
Inebilizumab/Inebilizumab
AQP4-IgG sero positive and sero negative participants will IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who enter OLP will receive IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants will have choice to enter in the SFP at any point during RCP or OLP and will be free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants will continue in the SFP for 12 months from last dose of study drug.
干预措施: Placebo (Other)
结局指标
主要结局
Time to Adjudication Committee (AC)-Determined Neuromyelitis Optica Spectrum Disorder (NMOSD) Attack During RCP
时间窗: Day 1 (Baseline) through Day 197
The NMOSD attack is defined as the presence of new or worsening symptom(s) related to NMOSD that meet at least one of the 18 protocol-defined attack criteria. These criteria were developed in conjunction with a panel of disease experts and with Food and Drug Administration input, and were intended to be clinically meaningful, objective, quantifiable, and able to be used worldwide. Only attacks positively adjudicated by the AC were used for the primary analysis.
次要结局
- Annualized AC-determined NMOSD Attack Rate During Any Exposure to Inebilizumab(For participants randomized to inebilizumab: Day 1 of RCP through end of OLP (approximately 3.5 years); and for participants randomized to placebo: Day 1 of OLP through the end of OLP (approximately 3 years))
- Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP(Day 1 (Baseline) through Day 197)
- Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP(Day 198 through end of OLP (maximum of 3 years after the last participant enters, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years))
- Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the Last Visit of RCP(Day 1 (Baseline) through Day 197)
- Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the Last Visit of RCP(Day 1 (Baseline) through Day 197)
- Cumulative Number of Active Magnetic Resonance Imaging (MRI) Lesions During RCP(From Screening (Day -28) to Day 197)
- Maximum Observed Serum Concentration (Cmax) of Inebilizumab (During RCP)(Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197))
- Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP)(Pre and post dose on Day 1; and on Days 92, 183, 274, and then every 6 months (maximum of 3 years after the last participant enters, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years))
- Number of Participants With TEAEs and TESAEs During SFP (Open-label Population)(Every 3 months for a total of 1 year after the last dose of study drug (approximately 3 years))
- Number of Participants With TEAEs and TESAEs During OLP(Day 198 through end of OLP period (maximum of 3 years after the last participant entered, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years))
- Number of Participants With TEAEs and TESAEs During SFP (Non-OLP Population)(Every 3 months for a total of 1 year after the last dose of study drug (approximately 3 years))
- Number of NMOSD-related In-patient Hospitalizations During RCP(Day 1 (Baseline) through Day 197)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) During RCP(Day 1 (Baseline) through Day 197)
- Time to Maximum Serum Concentration (Tmax) of Inebilizumab (During RCP)(Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197))
- Area Under the Serum Concentration Time Curve of the Dosing Interval (AUC0-14d) of Inebilizumab (During RCP)(Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197))
- Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP)(Pre and post dose on Day 1; and on Days 29, 85, and 197)